41 results on '"Pigment Epithelium of Eye cytology"'
Search Results
2. Replacement of the RPE monolayer.
- Author
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Sheridan CM, Mason S, Pattwell DM, Kent D, Grierson I, and Williams R
- Subjects
- Animals, Humans, Iris cytology, Iris transplantation, Macular Degeneration pathology, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye embryology, Stem Cell Transplantation, Cell Transplantation methods, Macular Degeneration surgery, Pigment Epithelium of Eye transplantation
- Abstract
There are numerous scenarios in which replacing the diseased RPE monolayer is an attractive but as yet unrealised goal. The proof of concept that vision can be improved by placing a healthy neuroretina onto a different, healthy, underlying RPE layer is demonstrated in patch graft transplantations. The surgical procedure to relocate the neuroretina is both complex and is hampered by postoperative complications and as such newer replacement procedures are also being investigated including stem cell replacement therapies. Past studies have largely focused on using cell suspensions and have had disappointing outcomes largely due to the lack of control over cellular differentiation, incomplete attachment onto Bruch's membrane and subsequent integration into the existing RPE monolayer. The choice of which cells to transplant is still under investigation and is complicated by factors such as the ease of collection of an adequate sample, rejection following implantation, the age of the cells and ethical issues. In all these situations, however, understanding the mechanisms of cellular differentiation are likely to be prerequisite to future successes.The current research into replacing the RPE monolayer is briefly discussed with reference to our experiences comparing IPE and RPE cells in an in vitro environment.
- Published
- 2009
- Full Text
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3. Toll-like receptor 3 and geographic atrophy in age-related macular degeneration.
- Author
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Yang Z, Stratton C, Francis PJ, Kleinman ME, Tan PL, Gibbs D, Tong Z, Chen H, Constantine R, Yang X, Chen Y, Zeng J, Davey L, Ma X, Hau VS, Wang C, Harmon J, Buehler J, Pearson E, Patel S, Kaminoh Y, Watkins S, Luo L, Zabriskie NA, Bernstein PS, Cho W, Schwager A, Hinton DR, Klein ML, Hamon SC, Simmons E, Yu B, Campochiaro B, Sunness JS, Campochiaro P, Jorde L, Parmigiani G, Zack DJ, Katsanis N, Ambati J, and Zhang K
- Subjects
- Animals, Apoptosis, Case-Control Studies, Choroidal Neovascularization genetics, Genotype, Humans, In Vitro Techniques, Interferon Inducers pharmacology, Mice, Mice, Knockout, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye drug effects, Pigment Epithelium of Eye pathology, Poly I-C pharmacology, Polymorphism, Single Nucleotide, RNA, Double-Stranded adverse effects, RNA, Small Interfering adverse effects, RNA, Viral adverse effects, Macula Lutea pathology, Macular Degeneration genetics, Macular Degeneration pathology, Toll-Like Receptor 3 genetics
- Abstract
Background: Age-related macular degeneration is the most common cause of irreversible visual impairment in the developed world. Advanced age-related macular degeneration consists of geographic atrophy and choroidal neovascularization. The specific genetic variants that predispose patients to geographic atrophy are largely unknown., Methods: We tested for an association between the functional toll-like receptor 3 gene (TLR3) variant rs3775291 (involving the substitution of phenylalanine for leucine at amino acid 412) and age-related macular degeneration in Americans of European descent. We also tested for the effect of TLR3 Leu and Phe variants on the viability of human retinal pigment epithelial cells in vitro and on apoptosis of retinal pigment epithelial cells from wild-type mice and Tlr3-knockout (Tlr3(-/-)) mice., Results: The Phe variant (encoded by the T allele at rs3775291) was associated with protection against geographic atrophy (P=0.005). This association was replicated in two independent case-control series of geographic atrophy (P=5.43x10(-4) and P=0.002). No association was found between TLR3 variants and choroidal neovascularization. A prototypic TLR3 ligand induced apoptosis in a greater fraction of human retinal pigment epithelial cells with the Leu-Leu genotype than those with the Leu-Phe genotype and in a greater fraction of wild-type mice than Tlr3(-/-) mice., Conclusions: The TLR3 412Phe variant confers protection against geographic atrophy, probably by suppressing the death of retinal pigment epithelial cells. Since double-stranded RNA (dsRNA) can activate TLR3-mediated apoptosis, our results suggest a role of viral dsRNA in the development of geographic atrophy and point to the potential toxic effects of short-interfering-RNA therapies in the eye., (2008 Massachusetts Medical Society)
- Published
- 2008
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4. Evaluation of adenovirus-delivered human CD59 as a potential therapy for AMD in a model of human membrane attack complex formation on murine RPE.
- Author
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Ramo K, Cashman SM, and Kumar-Singh R
- Subjects
- Adenoviridae, Adult, Aging, Animals, CD59 Antigens administration & dosage, Cell Culture Techniques, Cell Line, Embryo, Mammalian, Flow Cytometry, Genetic Vectors, Humans, Macular Degeneration physiopathology, Mice, Mice, Inbred C57BL, Models, Biological, Pigment Epithelium of Eye cytology, CD59 Antigens therapeutic use, Complement Membrane Attack Complex physiology, Macular Degeneration drug therapy, Pigment Epithelium of Eye physiology
- Abstract
Purpose: Complement-mediated damage to the retinal pigment epithelium (RPE), Bruch membrane, and choroid has been associated with pathogenesis in age-related macular degeneration (AMD). The terminal step of complement activation involves lysis of cells by the insertion of the membrane attack complex (MAC) in the plasma membrane. The hypothesis that local overexpression of human CD59 (hCD59) delivered by an adenovirus (Ad) vector to primary murine RPE cells in vitro, RPE in vivo, or cornea ex vivo protects those cells from human MAC deposition and lysis was tested., Methods: A humanized model of MAC deposition on murine cells and murine ocular tissues including RPE and cornea was developed to permit testing of human complement regulators in mice. A recombinant adenovirus-expressing hCD59 was generated, and this virus was injected into the subretinal space of adult mice. Subsequently, eyecups from these mice were exposed to human serum, and the levels of MAC deposition on the RPE were quantified. hCD59 was also expressed on murine cornea ex vivo and in murine hepatocytes, and primary RPE cells in vitro and levels of human MAC deposition and cell lysis were measured., Results: Adenovirus-mediated delivery of hCD59 to the RPE, cornea, or cells in culture protects those cells from human MAC deposition and MAC-mediated damage and vesiculation., Conclusions: The humanized model of MAC deposition on murine ocular tissues allows testing of human complement regulators that may have potential in the treatment of AMD or other diseases associated with complement activation.
- Published
- 2008
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5. Spatial cues for the enhancement of retinal pigment epithelial cell function in potential transplants.
- Author
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Lee CJ, Fishman HA, and Bent SF
- Subjects
- Aging, Cell Line, Cell Membrane metabolism, Epithelial Cells metabolism, Humans, Microscopy, Fluorescence methods, Phagocytosis, Polyesters chemistry, Time Factors, Cell Transplantation methods, Epithelial Cells cytology, Macular Degeneration pathology, Pigment Epithelium of Eye cytology, Retina cytology
- Abstract
Retinal pigment epithelial (RPE) cellular morphology and function are vital to the health of the retina. In age-related macular degeneration, RPE dysfunction and changes in Bruch's membrane occur. Thus, a potential cure is a dual-layer biomimetic transplant consisting of a layer of healthy RPE cells cultured on a support membrane. In this study, we investigated human anterior lens capsule as a replacement for Bruch's membrane and also explored different seeding methods as ways of inducing the desired cellular morphology and function. Using in vitro assays, we demonstrated that RPE cells cultured on lens capsule exhibited epithelial characteristics, such as the presence of actin belts and the formation of tight junctions in the monolayer. Bovine photoreceptor outer segments were also incubated with the RPE cells in order to quantify the binding and ingestion activity of the RPE cells. With these assays, we determined that cells seeded by centrifugation appeared to possess the most epithelial-like morphology, with the shortest overall length and the smallest elongation. They also exhibited enhanced metabolic activity, with a 1.5-fold increase over conventional gravity seeding. Thus, the spatial cues provided by centrifugation may assist cells in assuming native RPE function. Therefore, a dual-layer transplant, with RPE cells organized by centrifugation onto lens capsule, appears promising in achieving native retinal function.
- Published
- 2007
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6. Proteomic and phototoxic characterization of melanolipofuscin: correlation to disease and model for its origin.
- Author
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Warburton S, Davis WE, Southwick K, Xin H, Woolley AT, Burton GF, and Thulin CD
- Subjects
- Adult, Aged, Cytoplasmic Granules ultrastructure, Humans, Immunoblotting, Lipofuscin metabolism, Melanosomes ultrastructure, Photoreceptor Cells metabolism, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye metabolism, Proteome isolation & purification, Rhodopsin metabolism, Spectrometry, Fluorescence, Lipofuscin toxicity, Macular Degeneration pathology, Melanosomes metabolism, Models, Biological, Proteomics
- Abstract
Purpose: Melanolipofuscin (MLF) is a complex granule, exhibiting properties of both melanosomes and lipofuscin (LF) granules, which accumulates in retinal pigment epithelial (RPE) cells and may contribute to the etiology of age-related macular degeneration (AMD). MLF accumulation has been reported by Feeney-Burns to more closely reflect the onset of AMD than the accumulation of lipofuscin. In an effort to assess the possible contribution MLF may have to the onset of AMD, we analyzed the phototoxicity and protein composition of MLF and compared those results to that of LF., Methods: Specifically, we observed the accumulation of MLF in human RPE from different decades of life, and assessed the phototoxicity of these granules. We also employed fluorescence spectroscopy, atomic force microscopy, transmission and scanning electron microscopy and proteomic analysis to examine the composition of MLF granules in an effort to ascertain their origin., Results: Our results show that MLF granules are phototoxic and their accumulation more closely reflects the onset of AMD than does LF accumulation. Our compositional analysis of MLF has shown that while these granules contain some similarities to LF granules, MLF is substantially different. Of significant interest is the finding that MLF, in contrast to LF, does not contain photoreceptor-specific proteins, suggesting that MLF may not originate from the phagocytosis of photoreceptor outer segments. Instead the presence of RPE- and melanosome-specific proteins would suggest that MLF accumulates as a result of the melanosomal autophagocytosis of RPE cells., Conclusions: Our results provide significant insight into understanding the formation and toxicity of MLF and suggest a possible contribution to the etiology of retinal diseases.
- Published
- 2007
7. Carboxyethylpyrrole oxidative protein modifications stimulate neovascularization: Implications for age-related macular degeneration.
- Author
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Ebrahem Q, Renganathan K, Sears J, Vasanji A, Gu X, Lu L, Salomon RG, Crabb JW, and Anand-Apte B
- Subjects
- Aged, 80 and over, Allantois blood supply, Animals, Bruch Membrane chemistry, Cell Culture Techniques, Cell Line, Cells, Cultured, Chick Embryo, Child, Chorion blood supply, Choroidal Neovascularization etiology, Dose-Response Relationship, Drug, Humans, Laser Coagulation, Mice, Mice, Inbred C57BL, Middle Aged, Neovascularization, Physiologic, Oxidation-Reduction, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye drug effects, Pigment Epithelium of Eye metabolism, Pyrroles metabolism, Rats, Rats, Sprague-Dawley, Serum Albumin chemistry, Vascular Endothelial Growth Factor A analysis, Vascular Endothelial Growth Factor A metabolism, Choroidal Neovascularization metabolism, Macular Degeneration metabolism, Pyrroles chemistry, Pyrroles pharmacology
- Abstract
Choroidal neovascularization (CNV), the advanced stage of age-related macular degeneration (AMD), accounts for >80% of vision loss in AMD. Carboxyethylpyrrole (CEP) protein modifications, uniquely generated from oxidation of docosahexaenoate-containing lipids, are more abundant in Bruch's membrane from AMD eyes. We tested the hypothesis that CEP protein adducts stimulate angiogenesis and possibly contribute to CNV in AMD. Human serum albumin (HSA) or acetyl-Gly-Lys-O-methyl ester (dipeptide) were chemically modified to yield CEP-modified HSA (CEP-HSA) or CEP-dipeptide. The in vivo angiogenic properties of CEP-HSA and CEP-dipeptide were demonstrated by using the chick chorioallantoic membrane and rat corneal micropocket assays. Low picomole amounts of CEP-HSA and CEP-dipeptide stimulated neovascularization. Monoclonal anti-CEP antibody neutralized limbal vessel growth stimulated by CEP-HSA, whereas anti-VEGF antibody was found to only partially neutralize vessel growth. Subretinal injections of CEP-modified mouse serum albumin exacerbated laser-induced CNV in mice. In vitro treatments of human retinal pigment epithelial cells with CEP-dipeptide or CEP-HSA did not induce increased VEGF secretion. Overall, these results suggest that CEP-induced angiogenesis utilizes VEGF-independent pathways and that anti-CEP therapeutic modalities might be of value in limiting CNV in AMD.
- Published
- 2006
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8. Synergic effect of polymorphisms in ERCC6 5' flanking region and complement factor H on age-related macular degeneration predisposition.
- Author
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Tuo J, Ning B, Bojanowski CM, Lin ZN, Ross RJ, Reed GF, Shen D, Jiao X, Zhou M, Chew EY, Kadlubar FF, and Chan CC
- Subjects
- Animals, Case-Control Studies, Complement Factor H genetics, Complement Factor H metabolism, DNA Helicases metabolism, DNA Repair Enzymes, Genes, Reporter, Genetic Predisposition to Disease, Humans, Lymphocytes cytology, Lymphocytes metabolism, Macular Degeneration pathology, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye metabolism, Poly-ADP-Ribose Binding Proteins, Retina cytology, Retina metabolism, 5' Flanking Region, Aging, DNA Helicases genetics, Macular Degeneration genetics, Polymorphism, Single Nucleotide
- Abstract
This study investigates age-related macular degeneration (AMD) genetic risk factors through identification of a functional single-nucleotide polymorphism (SNP) and its disease association. We chose ERCC6 because of its roles in the aging process, DNA repair, and ocular degeneration from the gene disruption. Bioinformatics indicated a putative binding-element alteration on the sequence containing C-6530>G SNP in the 5' flanking region of ERCC6 from Sp1 on the C allele to SP1, GATA-1, and OCT-1 on the G allele. Electrophoretic mobility shift assays displayed distinctive C and G allele-binding patterns to nuclear proteins. Luciferase expression was higher in the vector construct containing the G allele than that containing the C allele. A cohort of 460 advanced AMD cases and 269 age-matched controls was examined along with pathologically diagnosed 57 AMD and 18 age-matched non-AMD archived cases. ERCC6 C-6530>G was associated with AMD susceptibility, both independently and through interaction with an SNP (rs380390) in the complement factor H (CFH) intron reported to be highly associated with AMD. A disease odds ratio of 23 was conferred by homozygozity for risk alleles at both ERCC6 and CFH compared with homozygozity for nonrisk alleles. Enhanced ERCC6 expression was observed in lymphocytes from healthy donors bearing ERCC6 C-6530>G alleles. Intense immunostaining of ERCC6 was also found in AMD eyes from ERCC6 C-6530>G carriers. The strong AMD predisposition conferred by the ERCC6 and CFH SNPs may result from biological epistasis, because ERCC6 functions in universal transcription as a component of RNA pol I transcription complex.
- Published
- 2006
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9. Age-related macular degeneration (AMD): pathogenesis and therapy.
- Author
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Nowak JZ
- Subjects
- Angiogenesis Inhibitors therapeutic use, Antioxidants therapeutic use, Choroidal Neovascularization etiology, Genetic Predisposition to Disease, Humans, Laser Coagulation, Lipofuscin metabolism, Macular Degeneration genetics, Photochemotherapy methods, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye physiopathology, Retinal Drusen etiology, Macular Degeneration etiology, Macular Degeneration therapy
- Abstract
Age-related macular degeneration (AMD) is a disease leading to severe visual loss and legal blindness in the elderly population. Its pathogenesis, likely multifactorial, involving a complex interaction of metabolic, functional, genetic and environmental factors, remains poorly understood. For these reasons currently used therapeutic approaches are insufficiently effective. Although major abnormalities are seen in four functionally interrelated tissues, i.e., photoreceptors, retinal pigment epithelium (RPE), Bruch's membrane and choriocapillaries, the impairment of RPE cell functions is an early and crucial event in the molecular pathways leading to clinically relevant AMD changes. RPE progressively degenerate, which results in a progressive irreversible degeneration of photoreceptors. Four processes: lipofuscinogenesis, drusogenesis, inflammation and neovascularization, specifically contribute to the development of two forms of AMD, the dry form (non-exudative; geographic atrophy) and the wet form (exudative, neovascular). This paper briefly describes major molecular and cellular events leading to AMD, and presents currently used and new experimental, forthcoming therapeutic strategies.
- Published
- 2006
10. Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers.
- Author
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Luibl V, Isas JM, Kayed R, Glabe CG, Langen R, and Chen J
- Subjects
- Adult, Aged, Aged, 80 and over, Amyloid toxicity, Cells, Cultured, Female, Fetus anatomy & histology, Humans, Male, Middle Aged, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye metabolism, Pigment Epithelium of Eye pathology, Retinal Drusen pathology, Aging physiology, Amyloid chemistry, Macular Degeneration pathology, Protein Conformation, Protein Folding, Retinal Drusen metabolism
- Abstract
Protein misfolding and aggregation are thought to underlie the pathogenesis of many amyloid diseases, such as Alzheimer and Parkinson diseases, whereby a stepwise protein misfolding process begins with the conversion of soluble protein monomers to prefibrillar oligomers and progresses to the formation of insoluble amyloid fibrils. Drusen are extracellular deposits found in aging eyes and in eyes afflicted with age-related macular degeneration (AMD). Recent characterizations of drusen have revealed protein components that are shared with amyloid deposits. However, characteristic amyloid fibrils have thus far not been identified in drusen. In this study, we tested the hypothesis that nonfibrillar oligomers may be a common link in amyloid diseases. Oligomers consisting of distinct amyloidogenic proteins and peptides can be detected by a recently developed antibody that is thought to recognize a common structure. Notably, oligomers exhibit cellular toxicity, which suggests that they play a role in the pathogenesis of neurodegenerative diseases. Through use of the anti-oligomer antibody, we came to observe the presence of nonfibrillar, toxic oligomers in drusen. Conversely, no reactivity was observed in age-matched control eyes without drusen. These results suggest that amyloid oligomers may be involved in drusen biogenesis and that similar protein misfolding processes may occur in AMD and amyloid diseases.
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- 2006
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11. Iris pigment epithelial translocation in the treatment of exudative macular degeneration: a 3-year follow-up.
- Author
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Aisenbrey S, Lafaut BA, Szurman P, Hilgers RD, Esser P, Walter P, Bartz-Schmidt KU, and Thumann G
- Subjects
- Adult, Aged, Aged, 80 and over, Choroidal Neovascularization etiology, Choroidal Neovascularization physiopathology, Choroidal Neovascularization surgery, Exudates and Transudates, Female, Fluorescein Angiography, Follow-Up Studies, Humans, Macular Degeneration complications, Male, Middle Aged, Ophthalmoscopy, Pigment Epithelium of Eye cytology, Transplantation, Autologous, Visual Field Tests, Cell Transplantation, Graft Survival physiology, Iris cytology, Macular Degeneration physiopathology, Macular Degeneration surgery, Pigment Epithelium of Eye transplantation, Visual Acuity physiology
- Abstract
Objective: To report the functional and anatomical outcome of 20 patients who underwent surgical removal of choroidal neovascularization combined with transplantation of autologous iris pigment epithelial cells to the subretinal space 3 years after treatment., Methods: Freshly isolated autologous iris pigment epithelial cells were translocated to the subretinal space in 20 patients after membrane extraction. Patients were followed up by funduscopy, angiography, microperimetry, and visual acuity testing., Results: After a follow-up of 3 years, 1 patient showed improved visual acuity, 13 patients retained stable visual acuity, and 3 patients had reduced visual acuity. No macular edema or recurrent choroidal neovascularization was apparent at any time during the follow-up., Conclusions: Transplanted autologous iris pigment epithelial cells were well tolerated for 3 years and stabilization of visual acuity was achieved in most patients. These results suggest that iris pigment epithelial cells may serve as a substitute for retinal pigment epithelial cells after choroidal neovascularization removal in patients with exudative macular degeneration; however, whether these cells will be of any value for the restoration of vision and possible protection against choroidal neovascularization recurrence awaits further clinical observation and additional research.
- Published
- 2006
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12. Molecular composition of drusen and possible involvement of anti-retinal autoimmunity in two different forms of macular degeneration in cynomolgus monkey (Macaca fascicularis).
- Author
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Umeda S, Suzuki MT, Okamoto H, Ono F, Mizota A, Terao K, Yoshikawa Y, Tanaka Y, and Iwata T
- Subjects
- Aging, Animals, Annexin A2 chemistry, Autoantibodies chemistry, Autoantigens chemistry, Autoimmunity, Blotting, Western, Cells, Cultured, Chromatography, Liquid, Complement Activation, Crystallins chemistry, Dogs, Electrophoresis, Gel, Two-Dimensional, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunohistochemistry, Macaca fascicularis, Mass Spectrometry, Microscopy, Fluorescence, Models, Biological, Pigment Epithelium of Eye cytology, Proteomics, Retina immunology, Retina metabolism, Retinal Drusen metabolism, Time Factors, mu-Crystallins, Macular Degeneration pathology, Retina pathology, Retinal Drusen genetics
- Abstract
We have previously reported a cynomolgus monkey (Macaca fascicularis) pedigree with early onset macular degeneration that develops drusen at 2 yr after birth. In this study, the molecular composition of drusen in monkeys affected with late onset and early onset macular degeneration was both characterized. Involvement of anti-retinalautoimmunity in the deposition of drusen and the pathogenesis of the disease was also evaluated. Funduscopic and histological examinations were performed on 278 adult monkeys (mean age=16.94 yr) for late onset macular degeneration. The molecular composition of drusen was analyzed by immunohistochemistry and/or direct proteome analysis using liquid chromatography tandem mass spectroscopy (LC-MS/MS). Anti-retinal autoantibodies in sera were screened in 20 affected and 10 age-matched control monkeys by Western blot techniques. Immunogenic molecules were identified by 2D electrophoresis and LC-MS/MS. Relative antibody titer against each antigen was determined by ELISA in sera from 42 affected (late onset) and 41 normal monkeys. Yellowish-white spots in the macular region were observed in 90 (32%) of the late onset monkeys that were examined. Histological examination demonstrated that drusen or degenerative retinal pigment epithelium (RPE) cells were associated with the pigmentary abnormalities. Drusen in both late and early onset monkeys showed immunoreactivities for apolipoprotein E, amyloid P component, complement component C5, the terminal C5b-9 complement complex, vitronectin, and membrane cofactor protein. LC-MS/MS analyses identified 60 proteins as constituents of drusen, including a number of common components in drusen of human age-related macular degeneration (AMD), such as annexins, crystallins, immunoglobulins, and complement components. Half of the affected monkeys had single or multiple autoantibodies against 38, 40, 50, and 60 kDa retinal proteins. The reacting antigens of 38 and 40 kDa were identified as annexin II and mu-crystallin, respectively. Relative antibody titer against annexin II in affected monkeys was significantly higher than control animals (P<0.01). Significant difference was not observed in antibody titer against mu-crystallin; however, several affected monkeys showed considerably elevated titer (360-610%) compared with the mean for unaffected animals. Monkey drusen both in late and early onset forms of macular degeneration had common components with drusen in human AMD patients, indicating that chronic inflammation mediated by complement activation might also be involved in the formation of drusen in these affected monkeys. The high prevalence of anti-retinalautoantibodies in sera from affected monkeys demonstrated an autoimmune aspect of the pathogenesis of the disease. Although further analyses are required to determine whether and how autoantibodies against annexin II or mu-crystallin relate to the pathogenesis of the disease, it could be hypothesized that immune responses directed against these antigens might trigger chronic activation of the complement cascade at the site of drusen formation.
- Published
- 2005
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13. Impaired RPE survival on aged submacular human Bruch's membrane.
- Author
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Gullapalli VK, Sugino IK, Van Patten Y, Shah S, and Zarbin MA
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Cattle, Cell Adhesion physiology, Cell Nucleus ultrastructure, Cell Size, Cell Survival physiology, Child, Child, Preschool, Extracellular Matrix ultrastructure, Fetus cytology, Humans, Infant, Infant, Newborn, Microscopy, Electron, Scanning, Middle Aged, Organ Culture Techniques, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye ultrastructure, Aging pathology, Bruch Membrane ultrastructure, Macular Degeneration pathology, Pigment Epithelium of Eye transplantation
- Abstract
Resurfacing of diseased or iatrogenically damaged Bruch's membrane with healthy retinal pigment epithelium (RPE) has been proposed as adjunctive treatment for age-related macular degeneration (AMD). The purpose of this study was to determine whether cultured fetal human RPE cells can attach and differentiate on aged submacular human Bruch's membrane. Bruch's membrane was debrided to expose native RPE basement membrane, the superficial inner collagenous layer directly below the RPE basement membrane, or the deep inner collagenous layer. These are three surfaces that transplanted RPE cells will encounter in situ. Approximately 3146 cultured fetal RPE cells mm(-2) were seeded onto these three surfaces and grown in organ culture for 1, 7, or 14 days. Explants were bisected and examined histologically or analyzed with a scanning electron microscope. RPE nuclear density was measured on stained sections. Morphology and cell density were compared to cells seeded onto bovine corneal endothelial cell-extracellular matrix (BCE-ECM). In situ submacular RPE nuclear density was also measured in tissue sections of donor eyes ranging from 18 weeks gestation to 88 years of age to determine the effect of age on RPE density. Compared to cells seeded onto BCE-ECM at similar density, RPE cell coverage and cellular morphology on aged submacular human Bruch's membrane was poor at all time points. In contrast to cells on BCE-ECM, RPE cell density on Bruch's membrane decreased with time. In general, cell morphology on all three Bruch's membrane surfaces worsened by day-7 compared to day-1. Although some cells were more pigmented on RPE basement membrane and the deep inner collagenous layer at day-7, poor cellular morphology indicated the remaining cells were not well differentiated. At day-14, the cells were uniform and cuboidal on BCE-ECM, with cell density similar to that at day-7 and similar to in situ density of young donors (
- Published
- 2005
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14. Outcome of transplantation of autologous retinal pigment epithelium in age-related macular degeneration: a prospective trial.
- Author
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Binder S, Krebs I, Hilgers RD, Abri A, Stolba U, Assadoulina A, Kellner L, Stanzel BV, Jahn C, and Feichtinger H
- Subjects
- Aged, Aged, 80 and over, Cell Transplantation, Choroidal Neovascularization diagnosis, Choroidal Neovascularization etiology, Choroidal Neovascularization surgery, Electroretinography, Female, Fluorescein Angiography, Humans, Indocyanine Green, Macular Degeneration complications, Macular Degeneration diagnosis, Male, Middle Aged, Pigment Epithelium of Eye cytology, Prospective Studies, Tomography, Optical Coherence, Transplantation, Autologous, Treatment Outcome, Visual Acuity, Visual Fields, Macular Degeneration surgery, Pigment Epithelium of Eye transplantation
- Abstract
Purpose: To present the outcome of a consecutive series of patients who had foveal choroidal neovascularization (fCNV) in age-related macular degeneration (AMD) and were treated with subretinal surgery combined with simultaneous transplantation of autologous retinal pigment epithelial (RPE) cells., Methods: Patients with fCNV who were not eligible for laser or photodynamic therapy were included in the study. They underwent subretinal membrane excision with simultaneous transplantation of autologous RPE cells. Eyes with membrane excision alone served as the control. Tests included best corrected visual acuity for far and near with Early Treatment Diabetic Retinopathy Study (ETDRS) and Jaeger charts, multifocal (mf)ERG, central visual field analysis, optical coherence tomography (OCT), and angiography, before surgery, and 1 month and 3 months after treatment, and at 3-month intervals thereafter., Results: The results of final examinations of 53 eyes are presented. In 39 eyes, RPE transplantation was performed (group 1); 14 eyes had membrane excision alone (group 2). In group 1, visual acuity improved significantly, two or more lines in 21 (53.8%) patients; remained stable in 12 patients (30.8%); and decreased two or more lines in 6 patients (15.4%; P=0.0062). In group 2, the corresponding values were 21.1%, 57.8%, and 21.1% (P=0.5377 NS). Statistical analysis of results in the two groups showed a trend in favor of group 1 (P=0.9714). The difference in reading acuity was significant between the two groups (mean change in group 1: 1.85 +/- 0.42 vs. 0.43 +/- 0.47 in group 2; P=0.0001). mfERG response density changes were significantly different between groups 1 and 2 (P=0.0094). No significant decreases in central visual field defects were detected. OCT showed the postoperative median retinal thickness in the lesion area in group 1 to be higher (242.31 +/- 12.30 microm) than in group 2 (202.07 +/- 10.68 microm), showing a trend (P=0.0682)., Conclusions: Patients undergoing fCNV removal with autologous transplantation of RPE reached significantly better reading acuity and higher mfERG-response density than control subjects. The results provide evidence that autologous transplantation of RPE is a beneficial supplement to membrane excision alone in patients with fCNV in AMD and may be regarded as a reasonable treatment option.
- Published
- 2004
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15. Unexpected intracellular localization of the AMD-associated cystatin C variant.
- Author
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Paraoan L, Ratnayaka A, Spiller DG, Hiscott P, White MR, and Grierson I
- Subjects
- Aging, Alanine chemistry, Blotting, Western, Cell Nucleus metabolism, Cells, Cultured, Cystatins genetics, Cystatins metabolism, Cytoplasm metabolism, DNA Primers chemistry, Electrophoresis, Polyacrylamide Gel, Golgi Apparatus metabolism, Green Fluorescent Proteins metabolism, HeLa Cells, Humans, Microscopy, Confocal, Microscopy, Fluorescence, Mitochondria metabolism, Mitochondria pathology, Mutagenesis, Site-Directed, Mutation, Pigment Epithelium of Eye cytology, Plant Proteins, Plasmids metabolism, Protein Structure, Tertiary, Threonine chemistry, Time Factors, Transfection, Trypsin pharmacology, Cystatins biosynthesis, Macular Degeneration genetics
- Abstract
Cystatin C is abundantly expressed by the retinal pigment epithelium (RPE) of the eye. Targeting of cystatin C to the Golgi apparatus and processing through the secretory pathway of RPE cells are dependent upon a 26-amino acid signal sequence of precursor cystatin C. A variant with an alanine (A) to threonine (T) mutation in the penultimate amino acid of the signal sequence (A25T) was recently correlated with increased risk of developing exudative age-related macular degeneration. The biochemical consequence of the A25T mutation upon targeting of the protein is reported here. Targeting and trafficking of full-length mutant (A25T) precursor cystatin C-enhanced green fluorescent protein fusion protein were studied in living, cultured retinal pigment epithelial and HeLa cells. Confocal microscopy studies were substantiated by immunodetection. In striking contrast to wild-type precursor cystatin C fusion protein conspicuously targeted to the Golgi apparatus, the threonine variant was associated principally with mitochondria. Some diffuse fluorescence was also observed throughout the cytoplasm and nucleus (but not nucleoli). Secretion of fusion protein derived from the threonine variant was reduced by approximately 50% compared with that of the wild-type cystatin C fusion protein. Expression of the variant fusion protein did not appear to impair expression or secretion of endogenous cystatin C.
- Published
- 2004
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16. Differential gene expression of early and late passage retinal pigment epithelial cells.
- Author
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Wang XF, Cui JZ, Nie W, Prasad SS, and Matsubara JA
- Subjects
- Angiogenesis Inducing Agents metabolism, Cells, Cultured, Gene Expression Profiling methods, Humans, Macular Degeneration pathology, Oligonucleotide Array Sequence Analysis, Pigment Epithelium of Eye metabolism, Polymerase Chain Reaction methods, beta-Galactosidase metabolism, Cellular Senescence genetics, Gene Expression Regulation, Macular Degeneration metabolism, Pigment Epithelium of Eye cytology
- Abstract
We examined the gene expression profiles of retinal pigment epithelial (RPE) cells which were aged in vitro by repeated passage. RPE cells from human eyes were cultured to passage 3-5 (early passage) or 19-21 (late passage) and used to study gene expression profiles by cDNA microarray. Results from microarray analysis were further confirmed by real-time PCR. Microarray analysis showed gene expression changes among 588 known genes. The expression levels of 15 genes (2.6%) increased in late passage RPE cells, while 43 genes (7.3%) decreased using a two-fold criterion. These differentially expressed genes encompassed many functional classes. A small number of stress genes, such as clusterin, replication protein A and Ku80, were up-regulated. The down-regulated genes included many enzymes of energy and biomolecule metabolism as well as cell cycle proteins and cell adhesion proteins. Results from real-time PCR were generally consistent with microarray findings. The expression levels of the examined angiogenic factors were either unchanged or down-regulated. Comparing early (p=3-5) and late (p=9-12) passage RPE cells, several categories of differentially expressed genes were identified. However, there was no enhanced expression of known angiogenic factors.
- Published
- 2004
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17. Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells against photooxidative damage.
- Author
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Gao X and Talalay P
- Subjects
- Animals, Antioxidants metabolism, Cells, Cultured, DNA-Binding Proteins genetics, Gene Expression drug effects, Glutathione metabolism, Humans, Intracellular Signaling Peptides and Proteins, Isothiocyanates, Kelch-Like ECH-Associated Protein 1, Light adverse effects, Lipid Peroxidation drug effects, Macular Degeneration drug therapy, Macular Degeneration prevention & control, Mice, Mice, Knockout, NAD(P)H Dehydrogenase (Quinone) metabolism, NF-E2-Related Factor 2, Oxygen metabolism, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye physiology, Proteins genetics, Retinoids toxicity, Sulfoxides, Trans-Activators genetics, Transcriptional Activation drug effects, Anticarcinogenic Agents pharmacology, Macular Degeneration metabolism, Oxidative Stress drug effects, Pigment Epithelium of Eye drug effects, Thiocyanates pharmacology
- Abstract
The retinal pigment epithelial cell (RPE cell) layer protects the photoreceptors of the retina against oxidative stress. The decline of this capacity is believed to be a major factor in the impairment of vision in age-related macular degeneration. Exposure of human adult RPE cells to UV light at predominantly 320-400 nm (UVA light) in the presence of all-trans-retinaldehyde results in photooxidative cytotoxicity. Significant protection of RPE cells was obtained by prior treatment with phase 2 gene inducers, such as the isothiocyanate sulforaphane or a bis-2-hydroxybenzylideneacetone Michael reaction acceptor. The degree of protection was correlated with the potencies of these inducers in elevating cytoprotective glutathione levels and activities of NAD(P)H:quinone oxidoreductase. In embryonic fibroblasts derived from mice in which the genes for the transcription factor Nrf2, the repressor Keap1, or both Nrf2 and Keap1 were disrupted, the magnitude of resistance to photooxidative damage paralleled the basal levels of glutathione and NAD(P)H:quinone oxidoreductase in each cell type. Demonstration of protection of RPE cells against photooxidative damage by induction of phase 2 proteins may shed light on the role of oxidative injury in ocular disease. Moreover, the finding that dietary inducers provide indirect antioxidant protection suggests novel strategies for preventing chronic degenerative diseases, such as age-related macular degeneration.
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- 2004
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18. Comparison of the growth potential of retinal pigment epithelial cells obtained during vitrectomy in patients with age-related macular degeneration or complex retinal detachment.
- Author
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van Meurs JC, ter Averst E, Croxen R, Hofland L, and van Hagen PM
- Subjects
- Cell Division physiology, Cell Survival physiology, Cell Transplantation, Cells, Cultured, Humans, Pigment Epithelium of Eye physiology, Pigment Epithelium of Eye transplantation, Macular Degeneration surgery, Pigment Epithelium of Eye cytology, Retinal Detachment surgery, Vitrectomy
- Published
- 2004
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19. Basement membranes and artificial substrates in cell transplantation.
- Author
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Sheridan C, Williams R, and Grierson I
- Subjects
- Basement Membrane physiology, Cell Adhesion, Cell Differentiation, Extracellular Matrix physiology, Humans, Pigment Epithelium of Eye cytology, Bruch Membrane physiology, Cell Transplantation methods, Macular Degeneration surgery, Membranes, Artificial, Pigment Epithelium of Eye transplantation
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- 2004
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20. The many possible roles of stem cells in age-related macular degeneration.
- Author
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Caballero S, Sengupta N, Crafoord S, Lund R, Kruse FE, Young M, and Grant MB
- Subjects
- Humans, Macular Degeneration pathology, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye physiology, Macular Degeneration surgery, Pigment Epithelium of Eye transplantation, Stem Cell Transplantation, Stem Cells physiology
- Published
- 2004
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21. [Pathogenesis of choroidal neovascularization. Old concepts, new questions].
- Author
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Fauser S, Engelmann K, Krohne TU, Lappas A, Kirchhof B, and Joussen AM
- Subjects
- Age Factors, Angiogenesis Inhibitors therapeutic use, Animals, Anti-Inflammatory Agents therapeutic use, Cells, Cultured, Choroidal Neovascularization complications, Choroidal Neovascularization genetics, Choroidal Neovascularization physiopathology, Choroidal Neovascularization therapy, Choroiditis complications, Clinical Trials, Phase III as Topic, Controlled Clinical Trials as Topic, Disease Models, Animal, Endothelial Growth Factors antagonists & inhibitors, Endothelial Growth Factors therapeutic use, Eye Injuries complications, Haplorhini, Humans, Intercellular Signaling Peptides and Proteins therapeutic use, Interferon-gamma therapeutic use, Laser Therapy, Lymphokines antagonists & inhibitors, Lymphokines therapeutic use, Macula Lutea transplantation, Macular Degeneration therapy, Mice, Mice, Transgenic, Myopia complications, Photochemotherapy, Pigment Epithelium of Eye cytology, Rats, Retinal Neovascularization etiology, Retinal Neovascularization physiopathology, Risk Factors, Triamcinolone therapeutic use, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Choroidal Neovascularization etiology, Macular Degeneration complications
- Abstract
Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world but the pathogenesis remains poorly understood. Malfunction of the retinal pigment epithelium (RPE) plays a central role in the disease and leads to either choriodal atrophy or proliferation. This article reviews the current concepts of the development of choriodal atrophy and neovascularisation. Furthermore, available animal models and potential therapeutical targets are discussed.
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- 2003
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22. [The molecular mechanisms of neovascular age-related macular degeneration].
- Author
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Miller DW, Joussen AM, and Holz FG
- Subjects
- Aged, Angiogenesis Inhibitors immunology, Angiogenesis Inhibitors therapeutic use, Animals, Antibodies, Monoclonal immunology, Bruch Membrane physiopathology, Cells, Cultured, Choroidal Neovascularization etiology, Choroidal Neovascularization therapy, Cytokines physiology, Disease Models, Animal, Endothelial Growth Factors physiology, Endothelium cytology, Endothelium immunology, Genetic Therapy, Humans, Intercellular Signaling Peptides and Proteins physiology, Lymphokines physiology, Macula Lutea metabolism, Macula Lutea physiopathology, Macular Degeneration therapy, Neovascularization, Pathologic immunology, Neovascularization, Pathologic physiopathology, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye physiopathology, Proteins physiology, Proteins therapeutic use, Rats, Receptors, Cytokine physiology, Research, Serpins physiology, Serpins therapeutic use, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Choroidal Neovascularization physiopathology, Eye Proteins, Macular Degeneration physiopathology, Nerve Growth Factors
- Abstract
Age-related macular degeneration is the leading cause of irreversible vision loss in industrialized countries. While early forms of this disease with drusen and focal pigment alterations generally do not lead to relevant functional limitations, later forms of the disease, either through atrophy or choroidal neovascularization, are associated with significant visual impairment. A significant increase in knowledge about the molecular mechanisms of new vessel formation from the choriocapillaries has occurred over the past few years. This has already allowed for the clinical testing of pharmacological agents which inhibit the formation of new vessels in AMD. This article describes current research in the pathophysiology of choroidal neovascularization secondary to age-related macular degeneration.
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- 2003
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23. [Detergent-like effects of the lipofuscin retinoid component A2-E in retinal pigment epithelial cells].
- Author
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Schütt F, Bergmann M, Kopitz J, and Holz FG
- Subjects
- Aged, Cell Membrane metabolism, Cells, Cultured metabolism, Cellular Senescence, Culture Media, Humans, Lysosomes metabolism, Macular Degeneration metabolism, Microsomes, Mitochondria metabolism, Retinal Diseases metabolism, Retinal Pigments metabolism, Succinate Dehydrogenase metabolism, beta-N-Acetylhexosaminidases metabolism, Lipofuscin metabolism, Macular Degeneration etiology, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye metabolism, Retinoids metabolism
- Abstract
Purpose: Several lines of evidence suggest that excessive accumulation of lipofuscin in postmitotic retinal pigment epithelial (RPE) cells with age and in various hereditary retinal diseases, plays a pathogenetic role. The lipofuscin retinoid component A2-E (N-retinylidene-N-retinylethanolamine) inhibits lysosomal degradation. Here we sought to evaluate additional toxic mechanisms of A2-E, whereby possible detergent-like effects on various membranes in human RPE cells were investigated by latency measurements., Methods: A postnuclear supernatant prepared from cultured human RPE cells was used to isolate intact lysosomes by fractionation of cellular organelles in two sequential gradients. Destabilization of the lysosomal membrane was tested by incubating the purified lysosomal fraction in the presence of A2-E and subsequent measurement of the latency of the lysosomal luminal marker beta-hexosaminidase. In order to compare the effect of A2-E on other cellular membranes, latencies of the specific markers succinate dehydrogenase and UDP-galactosyltransferase were assessed using partially purified mitochondria and microsomes. Intactness of the plasma membrane was tested by including A2-E in the culture medium before leakage of lactate dehydrogenase into the medium was determined., Results: A more than 100-fold purification of the lysosomal fraction was achieved. Except for a minor activity of the mitochondrial marker, no contamination with other cell fractions was observed. Intactness of the purified lysosomes was well preserved during incubation in isotonic media and provided the basis for investigations on a possible detergent-like action of A2-E on lysosomal integrity. At concentrations above 2 microM A2-E, progressive leakage of the lysosomal marker was observed. In comparison leakage of the mitochondrial marker was induced at significantly lower concentrations (1 microM), whereas ER/Golgi membranes and the plasma membrane were relatively insensitive to a detergent effect of the retinoid., Conclusions: The described practical and fast methodology to obtain highly purified and intact lysosomes from RPE cells, provides a very suitable tool for investigations on compounds affecting the lysosomal structure. The results suggest that A2-E causes disintegration of the lysosomal membrane at relatively low concentrations which may implicate an involvement of such a mechanism in triggering lipofuscin-induced dysfunction of aged RPE in vivo. Secondary to disintegration of the lysosomal membrane, damage to mitochondria might be an additional pathogenic mechanism. Our data provide evidence for surfactant-like properties of A2-E on biomembranes which might be operative in retinal diseases associated with excessive lipofuscin accumulation including age-related macular degeneration.
- Published
- 2002
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24. Autologous transplantation of genetically modified iris pigment epithelial cells: a promising concept for the treatment of age-related macular degeneration and other disorders of the eye.
- Author
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Semkova I, Kreppel F, Welsandt G, Luther T, Kozlowski J, Janicki H, Kochanek S, and Schraermeyer U
- Subjects
- Adenoviridae genetics, Animals, Cells, Cultured, Genetic Vectors, Green Fluorescent Proteins, Lasers, Luminescent Proteins metabolism, Microscopy, Fluorescence, Rats, Rats, Long-Evans, Rats, Wistar, Recombinant Fusion Proteins metabolism, Retina metabolism, Retinitis Pigmentosa therapy, Time Factors, Transplantation, Autologous, Aging, Cell Transplantation, Eye Diseases therapy, Iris cytology, Iris metabolism, Macular Degeneration therapy, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye metabolism
- Abstract
Age-related macular degeneration (ARMD) is the leading cause for visual impairment and blindness in the elder population. Laser photocoagulation, photodynamic therapy and excision of neovascular membranes have met with limited success. Submacular transplantation of autologous iris pigment epithelial (IPE) cells has been proposed to replace the damaged retinal pigment epithelium following surgical removal of the membranes. We tested our hypothesis that the subretinal transplantation of genetically modified autologous IPE cells expressing biological therapeutics might be a promising strategy for the treatment of ARMD and other retinal disorders. Pigment epithelium-derived factor (PEDF) has strong antiangiogenic and neuroprotective activities in the eye. Subretinal transplantation of PEDF expressing IPE cells inhibited pathological choroidal neovascularization in rat models of laser-induced rupture of Bruch's membrane and of oxygen induced ischemic retinopathy. PEDF expressing IPE transplants also increased the survival and preserved rhodopsin expression of photoreceptor cells in the RCS rat, a model of retinal degeneration. These findings suggest a promising concept for the treatment of ARMD and other retinal disorders.
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- 2002
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25. Transplantation of autologous retinal pigment epithelium in eyes with foveal neovascularization.
- Author
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Lois N
- Subjects
- Aged, Cataract Extraction, Choroidal Neovascularization etiology, Fovea Centralis pathology, Humans, Pigment Epithelium of Eye cytology, Tonometry, Ocular, Transplantation, Autologous, Treatment Outcome, Visual Acuity, Cell Transplantation methods, Choroidal Neovascularization surgery, Fovea Centralis surgery, Macular Degeneration complications, Pigment Epithelium of Eye transplantation
- Published
- 2002
- Full Text
- View/download PDF
26. Transplantation of autologous retinal pigment epithelium in eyes with foveal neovascularization.
- Author
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Stur M
- Subjects
- Choroidal Neovascularization etiology, Fovea Centralis pathology, Humans, Pigment Epithelium of Eye cytology, Tonometry, Ocular, Transplantation, Autologous, Treatment Outcome, Visual Acuity, Cell Transplantation methods, Choroidal Neovascularization surgery, Fovea Centralis surgery, Macular Degeneration complications, Pigment Epithelium of Eye transplantation
- Published
- 2002
- Full Text
- View/download PDF
27. Use of an oil-hydraulic microinjection pump for subretinal infusions.
- Author
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Weichel J, Valtink M, Engelmann K, and Richard G
- Subjects
- Animals, Cells, Cultured, Equipment Design, Feasibility Studies, Humans, Rats, Rats, Inbred Strains, Safety, Cell Transplantation instrumentation, Cell Transplantation methods, Infusion Pumps, Macular Degeneration surgery, Microinjections instrumentation, Pigment Epithelium of Eye cytology, Retina surgery
- Abstract
The injection of cell suspensions or drugs into the subretinal space is a new promising option of vitreoretinal surgery for the treatment of degenerative retinal disorders. We used a manual oil-hydraulic microinjection pump to subretinally inject suspensions of retinal pigment epithelial cells in Royal College of Surgeons rats and in patients suffering from age-related macular degeneration with geographic atrophy. The histological examination of the treated rat eyes showed that cell suspensions could be placed precisely in the subretinal space. Intra- and postoperative outcome of the patients in the clinical trial revealed no retinal complications during 6 months of follow up. We suggest the oil-hydraulic microinjection pump to be a valuable instrument for controlled and precisely dosed atraumatic infusion or aspiration of small volumes of cell suspensions, fluids or drugs in vitreoretinal surgery.
- Published
- 2002
28. Phosphatidylglycerol potently protects human retinal pigment epithelial cells against apoptosis induced by A2E, a compound suspected to cause age-related macula degeneration.
- Author
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Shaban H, Borrás C, Viña J, and Richter C
- Subjects
- Animals, Apoptosis drug effects, Cells, Cultured, Humans, Light, Middle Aged, Mitochondria drug effects, Mitochondria metabolism, Oxidative Stress drug effects, Pigment Epithelium of Eye drug effects, Pigment Epithelium of Eye metabolism, Rats, Rats, Wistar, Reactive Nitrogen Species metabolism, Reactive Oxygen Species metabolism, Ubiquinone pharmacology, Aging physiology, Apoptosis physiology, Macular Degeneration etiology, Phosphatidylglycerols pharmacology, Pigment Epithelium of Eye cytology, Pyridinium Compounds pharmacology, Retinoids pharmacology
- Abstract
Age-related macular degeneration (AMD) affects about one fifth of the population older than 65 years and is one of the main causes of poor vision in the elderly in industrialized nations. The endogenous lipophilic and cationic compound N-retinyl-N-retinylidene ethanolamine (A2E) is suspected to cause the dry form of the disease, which currently cannot be treated. The authors recently reported that A2E induces apoptosis in several cell types including porcine retinal pigment epithelial cells, detaches pro-apoptotic proteins from mitochondria, and inhibits cytochrome c oxidase. A2E acts primarily at the level of cardiolipin/cytochrome c oxidase, which in the light becomes permanently inactivated by A2E. The authors now report that A2E at low concentrations causes apoptosis in cultured human retinal pigment epithelial cells. These cells are more sensitive to A2E in the light than in the dark. Phosphatidylglycerol, a negatively charged phospholipid and immediate biosynthetic precursor of cardiolipin readily inhibits apoptosis. Exposure of cells to A2E results in the formation of reactive oxygen and nitrogen species, and exposure of mitochondria to A2E results in oxidative stress. Accordingly, the potent antioxidant coenzyme Q also protects cells against A2E-induced apoptosis. These findings are highly relevant for the treatment and/or prevention of AMD.
- Published
- 2002
- Full Text
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29. Expression of Sorsby's fundus dystrophy mutations in human retinal pigment epithelial cells reduces matrix metalloproteinase inhibition and may promote angiogenesis.
- Author
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Qi JH, Ebrahem Q, Yeow K, Edwards DR, Fox PL, and Anand-Apte B
- Subjects
- Animals, Cell Adhesion, Cell Division, Cell Line, Cell Movement, Cells, Cultured, Chick Embryo, Collagen metabolism, Collagen pharmacology, Cysteine chemistry, Drug Combinations, Genes, Dominant, Humans, Immunoblotting, Laminin pharmacology, Phenotype, Pigment Epithelium of Eye metabolism, Proteoglycans pharmacology, Serine chemistry, Tissue Inhibitor of Metalloproteinase-3 metabolism, Transfection, Epithelial Cells metabolism, Macular Degeneration genetics, Macular Degeneration metabolism, Matrix Metalloproteinase Inhibitors, Mutation, Neovascularization, Physiologic, Pigment Epithelium of Eye cytology, Retina cytology, Tissue Inhibitor of Metalloproteinase-3 genetics
- Abstract
Sorsby's fundus dystrophy (SFD) is an autosomal dominant degenerative disease of the macula caused by mutations in the tissue inhibitor of metalloproteinase-3 (TIMP-3) gene. Choroidal neovascularization is a hallmark of this disease, which closely resembles the exudative form of age-related macular degeneration. However, the mechanism by which TIMP-3 mutations induce the disease phenotype in SFD remains unknown. To address this question we established human retinal pigment epithelial cell lines expressing wild type or S156C (Ser(156) changed to cysteine) mutant TIMP-3. S156C TIMP-3 had reduced matrix metalloproteinase (MMP) inhibitory activity in retinal pigment epithelial cells and resulted in increased secretion and activation of gelatinase A and B. The conditioned medium from these cells induced angiogenesis in "in vivo" chick chorioallantoic membrane assays that could be reversed with recombinant wild type TIMP-3. Our data indicate that the choroidal neovascularization in SFD may be a result of increased MMP activity, which could lead to the stimulation of angiogenesis. These results also suggest the potential therapeutic use of TIMP-3 or synthetic MMP inhibitors in this disease.
- Published
- 2002
- Full Text
- View/download PDF
30. [Surgical procedures in the treatment of age-related macular degeneration].
- Author
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Walter P
- Subjects
- Age Factors, Cell Transplantation, Choroidal Neovascularization complications, Controlled Clinical Trials as Topic, Fibrinolytic Agents administration & dosage, Follow-Up Studies, Forecasting, Gases administration & dosage, Humans, Macular Degeneration drug therapy, Multicenter Studies as Topic, Pigment Epithelium of Eye cytology, Plasminogen Activators administration & dosage, Research, Retina surgery, Time Factors, Tissue Plasminogen Activator administration & dosage, Visual Acuity, Macula Lutea surgery, Macular Degeneration surgery, Ophthalmologic Surgical Procedures
- Abstract
The surgical techniques for removal of a subretinal membrane associated with age-related macular degeneration will be discussed and compared on the basis of published data. The so-called simple subretinal membrane extraction will be compared with pigment epithelium cell transplantation and with the various techniques for macular translocation. The pars plana gas injection with tissue plasminogen activator procedure will also be mentioned. Because a controlled trial with a sufficient number of patients and follow-up has not been carried out for any of these techniques, the results of published case series will be used for this review.
- Published
- 2002
- Full Text
- View/download PDF
31. Transplantation of autologous retinal pigment epithelium in eyes with foveal neovascularization resulting from age-related macular degeneration: a pilot study.
- Author
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Binder S, Stolba U, Krebs I, Kellner L, Jahn C, Feichtinger H, Povelka M, Frohner U, Kruger A, Hilgers RD, and Krugluger W
- Subjects
- Aged, Aged, 80 and over, Choroidal Neovascularization diagnosis, Choroidal Neovascularization etiology, Female, Fluorescein Angiography, Fovea Centralis pathology, Humans, Macular Degeneration diagnosis, Male, Middle Aged, Ophthalmologic Surgical Procedures, Pigment Epithelium of Eye cytology, Pilot Projects, Prospective Studies, Tonometry, Ocular, Transplantation, Autologous, Treatment Outcome, Visual Acuity, Visual Fields, Cell Transplantation methods, Choroidal Neovascularization surgery, Fovea Centralis surgery, Macular Degeneration complications, Pigment Epithelium of Eye transplantation
- Abstract
Purpose: To describe the indications, surgical technique, and clinical results of 14 eyes in 13 patients with age-related macular degeneration and foveal choroidal neovascularization, in which subretinal surgery was combined with simultaneous transplantation of autologous retinal pigment epithelial cells., Methods: Between March 1999 and February 2000, in a prospective study, 14 eyes (13 patients) with age-related macular degeneration underwent subretinal surgery because of foveal choroidal neovascularization with simultaneous transplantation of retinal pigment epithelium harvested from the nasal subretinal area of the same eye. Preoperatively, 1 month postoperatively, 3 months postoperatively and at 3-month intervals thereafter, examinations were performed including best-corrected visual acuity, visual field, biomicroscopy of anterior and posterior segment, tonometry, fluorescein and indocyanine angiographies, autofluorescence, scotometry, and fixation tests., Results: Postoperatively, after median observation of 17 months (range, 12 to 24 months) best-corrected visual acuity was improved 2 or more lines in eight eyes (57.1%), remained the same (+/- 1 line) in five eyes (35%), and decreased by more than 2 lines in one eye (7.1%). Pairwise t test showed significant improvement after 1 month (P = .0031, P = .0062) as well as 1 year (P = .0066, P = .0105). Satisfactory reading vision between Jaeger 1 and 4 was achieved in three eyes (21.2%). No significant intraoperative or postoperative complications occurred in any eye. No recurrence of choroidal neovascularization was observed during the observation period., Conclusions: In eyes with age-related macular degeneration and foveal choroidal neovascularization, autotransplantation of retinal pigment epithelium was performed in addition to conventional removal of the choroidal neovascularization without significant intraoperative or postoperative complications. Visual acuity improvement of 2 or more lines in 57% of the eyes was achieved. No recurrent choroidal neovascularization formation was observed during the observation period. The results of this pilot study suggest that autologous transplantation of retinal pigment epithelium combined with submacular surgery might be a reasonable treatment option for patients with foveal choroidal neovascularization secondary to age-related macular degeneration.
- Published
- 2002
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- View/download PDF
32. Visual function after removal of subretinal neovascular membranes in patients with age-related macular degeneration.
- Author
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Abe T, Yoshida M, Kano T, and Tamai M
- Subjects
- Aged, Aged, 80 and over, Choroidal Neovascularization etiology, Choroidal Neovascularization surgery, Female, Fibrosis, Fluorescein Angiography, Humans, Indocyanine Green, Macular Degeneration complications, Macular Degeneration surgery, Male, Middle Aged, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye physiology, Postoperative Care, Silicone Oils therapeutic use, Sulfur Hexafluoride therapeutic use, Visual Field Tests, Visual Fields, Vitrectomy, Choroidal Neovascularization physiopathology, Macular Degeneration physiopathology, Visual Acuity physiology
- Abstract
Background: Retinal pigment epithelial (RPE) cells have been transplanted to replace the RPE cells lost after surgical excision of choroidal neovascular membranes (CNV) associated with age-related macular degeneration. The purpose of this study was to analyze the visual function of eyes with altered RPE after surgical excision of choroidal neovascular membranes (CNV) associated with age-related macular degeneration, and to determine the effect of proliferated or migrated RPE cells on visual function., Methods: Forty-seven patients with age-related macular degeneration underwent excision of CNVs following vitrectomy and tamponade with sulfur hexafluoride (SF6) or silicone oil. The appearance of pre- or subretinal fibrosis and pigmentation of the lesion was considered to indicate proliferation and migration of RPE cells. Microperimetry was also performed., Results: A significant correlation was found between the size of CNVs removed by surgery and the size estimated by indocyanine green angiography (P=0.0126). The mean number of RPE cells lost was estimated at 1.52 x 10(4). Pre- or subretinal fibrosis or pigmentation was observed in 37 patients (75.5%). The number of eyes with fibrosis was significantly higher in eyes with silicone oil tamponade than with SF6 tamponade (P=0.0016). A statistically significant correlation was not found between the presence of fibrosis or pigmentation and the postoperative visual acuity. Not all patients used the area of pigmentation for fixation, and microperimetry showed that some of the patients had scotomas in well-pigmented areas., Conclusions: Fibrosis and pigmentation after excision of CNVs may not always indicate normal function in these areas. These observations are especially relevant for transplantation of pigment epithelial cells in the future.
- Published
- 2001
- Full Text
- View/download PDF
33. Retinal pigment epithelium translocation and central visual function in age related macular degeneration: preliminary results.
- Author
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Stanga PE, Kychenthal A, Fitzke FW, Halfyard AS, Chan R, Bird AC, and Aylward GW
- Subjects
- Aged, Aged, 80 and over, Cell Transplantation, Choroidal Neovascularization etiology, Choroidal Neovascularization physiopathology, Choroidal Neovascularization surgery, Feasibility Studies, Female, Fixation, Ocular, Fluorescein Angiography, Humans, Macular Degeneration complications, Male, Ophthalmoscopy, Photography, Pigment Epithelium of Eye cytology, Pilot Projects, Treatment Outcome, Visual Field Tests, Vitrectomy, Macular Degeneration physiopathology, Macular Degeneration surgery, Pigment Epithelium of Eye transplantation, Visual Acuity physiology
- Abstract
Purpose: To test the feasibility of a new surgical technique, and to assess visual function over the translocated retinal pigment epithelium (RPE) cells in patients operated upon for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD)., Materials and Methods: Six patients presenting previously untreated exudative AMD underwent surgical excision of the subfoveal CNV with RPE translocation and were followed from 1 to 10.5 months. The surgery consisted of a standard three port pars plana vitrectomy (TPPPV), excision of the CNV and RPE translocation. Pre and post-operative ocular examination included best-corrected visual acuity measurement, fundus color stereo photography and fundus fluorescein angiography. Optical coherence tomography (OCT) and confocal laser scanning ophthalmoscopy (cLSO) were performed post-operatively. A cross fixation target and a single-point flashing light were projected on different areas of the posterior pole using a cLSO. Photopic 10-2 perimetry, photopic fine matrix mapping, cLSO microperimetry were also performed pre and post-operatively in four patients. OCT cross-sectional scans and cLSO RPE autofluorescence were recorded to detect the presence of viable translocated RPE. Visual acuity, fixation, photopic 10-2 perimetry, photopic fine matrix mapping and cLSO microperimetry were tested for the presence of central visual function., Results: RPE could be effectively translocated at the time of CNV removal from the edge of the RPE defect to a subfoveal location. OCT showed the translocated RPE as an area of increased optical reflectivity with optical shadowing external to it. cLSO showed autofluorescence of the translocated RPE. The cross fixation target was seen when projected on the translocated RPE. During eccentric fixation, the patients could see a flashing point-target projected on the translocated RPE. Photopic 10-2 perimetry, photopic fine matrix mapping and cLSO microperimetry showed presence of central visual function., Conclusions: The authors propose that translocation of RPE at the time of CNV removal, from the edge of the RPE defect to a subfoveal location, may have a role in the surgical management of AMD.
- Published
- 2001
- Full Text
- View/download PDF
34. [New therapies for the treatment of age-related macular degeneration].
- Author
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Soubrane G, Kuhn D, Oubraham H, Quaranta M, and Coscas G
- Subjects
- Aged, Cell Transplantation, Choroidal Neovascularization diagnosis, Choroidal Neovascularization drug therapy, Choroidal Neovascularization prevention & control, Choroidal Neovascularization surgery, Choroidal Neovascularization therapy, Disease Progression, Fluorescein Angiography, Forecasting, Humans, Indocyanine Green, Laser Coagulation, Light Coagulation, Macular Degeneration drug therapy, Macular Degeneration etiology, Macular Degeneration pathology, Macular Degeneration surgery, Palliative Care, Photochemotherapy, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye transplantation, Porphyrins therapeutic use, Retinal Drusen pathology, Retinal Drusen therapy, Verteporfin, Visual Acuity, Macular Degeneration therapy
- Abstract
Age-related macular degeneration has a natural progression from the precursors (the drusen) towards atrophic or neovascular complications. Choroidal neovascularization is undoubtedly the aspect of the disease that benefits most from new therapeutical approaches. Destructive photocoagulation based on fluorescein angiography has demonstrated since 20 years its efficiency on choroidal neovascularization. The same approach based on indocyanine green (ICG) angiography would increase the number of patients available to therapy. Very recently photodynamic therapy has demonstrated its efficiency to stabilize visual acuity at least at two years in patients with choroidal new vessels predominantly well defined. Other treatment developments are considered, such as refinement of photocoagulation techniques or of surgery. Until now, none has demonstrated its efficiency although they raise justified hopes. The future approaches rely upon the progress of the research both in physiopathology of the disease and on the angiogenic process requiring a constant interaction with all thematics of research. Finally, palliative treatments will be required before heading up to a preventive treatment.
- Published
- 2001
35. Auto iris pigment epithelial cell transplantation in patients with age-related macular degeneration: short-term results.
- Author
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Abe T, Yoshida M, Tomita H, Kano T, Sato M, Wada Y, Fuse N, Yamada T, and Tamai M
- Subjects
- Aged, Aged, 80 and over, Automation, Electrophysiology, Epithelial Cells cytology, Female, Humans, Macular Degeneration physiopathology, Macular Degeneration surgery, Male, Middle Aged, Time Factors, Visual Acuity, Visual Fields, Aging physiology, Cell Transplantation methods, Iris cytology, Macular Degeneration therapy, Pigment Epithelium of Eye cytology
- Abstract
Autologous iris pigment epithelial cell transplantation was performed on patients with exudative age-related macular degeneration (AMD). Autologous IPE cell culture was performed using autologous serum after iridectomy in 7 patients with AMD. The cell suspensions (2 approximately 20 x 10(4) cells) were transplanted into the submacular lesion of individuals after removal of neovascular membranes. Subsequent ophthalmological examinations, including best corrected visual acuity and fluorescein or indocyanine green angiography, were performed. In addition, 15 patients with AMD, who underwent removal of neovascular membrane without transplantation, were evaluated as non randomized controls. Varying degrees of atrophy or defects of choriocapillaris and retinal pigment epithelium were observed in all of the patients. No cystoid macular edema or fluorescein leakage was observed after treatment, but window defects were present. No patient had decreased visual acuity. One treated patient developed mild subretinal fibrosis and an other patient developed mild preretinal fibrosis, however no difference was significant when compared with the control. In conclusion, the treatment resulted in no significant improvement in macular function, as compared with the control; however, no rejection or deterioration in visual acuity occurred up to the 13 month follow up.
- Published
- 2000
- Full Text
- View/download PDF
36. A potential role for immune complex pathogenesis in drusen formation.
- Author
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Johnson LV, Ozaki S, Staples MK, Erickson PA, and Anderson DH
- Subjects
- Acute-Phase Proteins immunology, Adolescent, Adult, Aged, Aged, 80 and over, Bruch Membrane cytology, Bruch Membrane immunology, Complement Membrane Attack Complex analysis, Complement Membrane Attack Complex immunology, Cytoplasm immunology, Humans, Immunoglobulin Fragments immunology, Immunoglobulins immunology, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye immunology, Polymerase Chain Reaction, Antigen-Antibody Complex immunology, Macular Degeneration immunology, Retinal Drusen immunology
- Abstract
Drusen are abnormal extracellular deposits that accumulate between the retinal pigmented epithelium and Bruch's membrane and are commonly associated with age-related macular degeneration. Our recent work has identified a number of plasma proteins as molecular components of drusen. Of interest is the fact that many of these drusen-associated molecules are acute phase reactant proteins and some have established roles in mediating immune responsiveness. As immune and inflammatory responses appear to play a role in the formation of other pathologic age-related deposits, we examined the distribution of immunoglobulin molecules and terminal complement complexes at sites of drusen deposition. Here, we report that concentrations of immunoglobulin G and terminal C5b-9 complement complexes are present in drusen. In addition, we observe that retinal pigmented epithelial cells overlying or directly adjacent to drusen, as well as some within apparently normal epithelia, exhibit cytoplasmic immunoreactivity for immunoglobulin and the C5 component of complement. Taken together, these results suggest that drusen biogenesis may be a byproduct of immune responsiveness, and they implicate immune complex-mediated pathogenesis involving retinal pigmented epithelial cells as an initiating event in drusen formation.
- Published
- 2000
- Full Text
- View/download PDF
37. Functional analysis after auto iris pigment epithelial cell transplantation in patients with age-related macular degeneration.
- Author
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Abe T, Yoshida M, Tomita H, Kano T, Nakagawa Y, Sato M, Wada Y, Fuse N, Yamada T, and Tamai M
- Subjects
- Aged, Aged, 80 and over, Cells, Cultured, Female, Humans, Macular Degeneration physiopathology, Male, Middle Aged, Transplantation, Autologous, Visual Fields, Cell Transplantation, Iris, Macular Degeneration surgery, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye transplantation
- Abstract
Recent transplantation studies indicate that subretinal space is not always an immunologically privileged site and non-autologous cells may be rejected in patients with exudative age-related macular degeneration (AMD). We performed autologous iris pigment epithelial (IPE) cell transplantation by cell suspension after autologous IPE cell culture in 8 patients with AMD. These patients were followed without immunosuppression between 1.5 and 8 months and the retinal function was analyzed. No cystoid macular edema or fluorescein leakage was observed. Six of the 8 patients improved visual acuity of more than two lines and the other two patients retained preoperative visual acuity. Five patients had increased visual field sensitivity, one patient retained pretransplantation sensitivity, and one patient showed a gradual decrease in sensitivity (one patient was not examined). Although 2 of the 8 patients showed decreased amplitude of flicker electroretinography (ERG) (about 60 to 70% as that of preoperative level), the average improvement of each amplitude of a single white flash (a wave), photopic, or flicker ERG was 123, 102, and 107%, respectively. No proliferative change in the submacular lesion or vitreous cavity was observed after transplantation. From this functional analysis, transplanted autologous IPE may have, in part, an alternative function in regard to the retinal pigment epithelium in the subretinal space.
- Published
- 1999
- Full Text
- View/download PDF
38. Allogenic fetal retinal pigment epithelial cell transplant in a patient with geographic atrophy.
- Author
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Weisz JM, Humayun MS, De Juan E Jr, Del Cerro M, Sunness JS, Dagnelie G, Soylu M, Rizzo L, and Nussenblatt RB
- Subjects
- Aged, Atrophy, Blindness etiology, Female, Fluorescein Angiography, Fundus Oculi, Graft Survival, Humans, Macular Degeneration complications, Macular Degeneration diagnosis, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye embryology, Transplantation, Homologous, Visual Acuity, Cell Transplantation, Fetal Tissue Transplantation methods, Macula Lutea pathology, Macular Degeneration surgery, Pigment Epithelium of Eye transplantation
- Abstract
Purpose: To test the hypothesis that healthy fetal retinal pigment epithelium (RPE) can rescue the remaining viable RPE and choriocapillaries and thereby the photoreceptors in non-neovascular age-related macular degeneration (ARMD) (geographic atrophy [GA])., Methods: A 65-year-old legally blind woman with non-neovascular ARMD underwent fetal RPE transplantation. Best-corrected visual acuity testing, detailed fundus examination, fundus photography, fluorescein angiography, scanning laser ophthalmoscope macular perimetry, and humoral and cellular immune response testing were performed. A suspension of RPE was infused into the subretinal space through a retinotomy along the superotemporal arcade at the edge of the area of GA. The patient did not take systemic immunosuppressants., Results: The patient's vision remained unchanged for 5 months after the surgery. Fluorescein angiography after transplantation showed leakage and staining at the level of the outer retina. There was progressive subretinal fibrosis in the area of the transplant. Immune response studies showed a weakly positive mixed lymphocyte response against phosducin and rhodopsin., Conclusion: Although it is surgically feasible to transplant fetal RPE to the subretinal space of patients with GA, such an allogenic RPE transplant without immunosuppression leads to leakage on fluorescein angiography and eventual fibrosis. A very weak immune response against proteins associated with photoreceptors is also of concern.
- Published
- 1999
- Full Text
- View/download PDF
39. In search of sight. Physicians in Chicago use fetal cells to combat a degenerative eye disease afflicting millions.
- Author
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Nash JM
- Subjects
- Chicago epidemiology, History, 20th Century, Humans, Macular Degeneration epidemiology, Patient Selection, Pigment Epithelium of Eye cytology, Research, Fetal Tissue Transplantation, Macular Degeneration therapy, Ophthalmology standards, Pigment Epithelium of Eye transplantation
- Published
- 1997
40. Morphologic changes in age-related maculopathy.
- Author
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Kliffen M, van der Schaft TL, Mooy CM, and de Jong PT
- Subjects
- Basement Membrane pathology, Basement Membrane ultrastructure, Bruch Membrane pathology, Bruch Membrane ultrastructure, Fluorescein Angiography, Humans, Macular Degeneration metabolism, Macular Degeneration therapy, Microscopy, Microscopy, Electron, Pigment Epithelium of Eye cytology, Retinal Drusen pathology, Macular Degeneration pathology, Pigment Epithelium of Eye ultrastructure
- Abstract
Age-related maculopathy (ARM) is a degenerative disorder of the central part of the retina with a rising prevalence in patients 50 years of age and older, and comprises different histopathological changes. The morphologic changes in ARM are described and illustrated with light-microscopical, electron microscopical, and fundus pictures. Furthermore, the most important biochemical data are given. The most prominent aging changes in early stages of ARM are drusen and basal laminar deposit (BLD), both extracellular deposits, that are assumed to be important in the development of ARM. Drusen accumulate within Bruch's membrane, whereas BLD is present between Bruch's membrane and the retinal pigment epithelium. Although the histopathologic characteristics of the deposits are well documented, the chemical composition has only been partly resolved. Biochemical analysis of these deposits is necessary to determine the source of the deposits and to find possible ways to avoid or treat them. The late stages of ARM, geographic atrophy, and neovascular (disciform) degeneration, are called age-related macular degeneration (AMD), and result in severe and irreversible visual impairment. Since there is still no adequate therapy for the majority of people disabled by AMD, and because of the aging population resulting in even more patients with this disease, it is necessary to intensify the research on ARM in order to prevent AMD or find a therapy for it.
- Published
- 1997
- Full Text
- View/download PDF
41. Transplantation of fetal retinal pigment epithelium in age-related macular degeneration with subfoveal neovascularization.
- Author
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Algvere PV, Berglin L, Gouras P, and Sheng Y
- Subjects
- Aged, Cell Membrane pathology, Cell Survival, Cells, Cultured, Female, Fluorescein Angiography, Fovea Centralis, Fundus Oculi, Humans, Macular Degeneration etiology, Macular Degeneration physiopathology, Middle Aged, Pigment Epithelium of Eye cytology, Pigment Epithelium of Eye embryology, Postoperative Complications, Visual Acuity, Visual Field Tests, Vitrectomy, Choroid blood supply, Fetal Tissue Transplantation, Macular Degeneration surgery, Neovascularization, Pathologic complications, Pigment Epithelium of Eye transplantation
- Abstract
Background: Age-related macular degeneration (ARMD) is caused by abnormal retinal pigment epithelium (RPE) and may be complicated by choroidal neovascularization. The object of treatment would be to replace the diseased RPE with normal human RPE., Method: Five patients with ARMD (preoperative visual acuity 0.08-0.2) underwent removal of subretinal fibrovascular membranes using pars plana vitrectomy techniques. Human fetal RPE (15-17 weeks gestational age) was cultured and transplanted as a monolayer patch into the subretinal space. Transplants were followed by funduscopy and fluorescein angiography. Macular function was assessed using scanning laser ophthalmoscopic (SLO) microperimetry., Results: Three RPE transplants were placed in the fovea; two were placed parafoveally. All transplants have survived for 3 months. They have grown and increased in size covering part of the epithelial defect caused by removal of the fibrovascular membrane. SLO microperimetry indicated that visual function was present in four of the transplants at 1 month but in only two at 3 months after surgery. Function over the transplants, especially those in the fovea, was compromised by cystoidlike macular edema., Conclusions: Human fetal RPE transplants survive well in the macula for as long as 3 months. They are capable of growing to cover epithelial defects caused by removal of subretinal neovascular membranes. The causes for development of macular edema in transplants directly in the fovea warrant further evaluation.
- Published
- 1994
- Full Text
- View/download PDF
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